It is now widely recognized that gender-based differences can play a major role in the predisposition to disease and injury, yet this remains an understudied phenomenon. Adolescent females who participate in jumping and pivoting sports suffer anterior cruciate ligament (ACL) injury at a 4 to 6-fold greater rate than adolescent males participating in the same sports. The reason(s) for this ACL injury disparity remain(s) obscure. Prior to puberty, male and female injury risk appears equal. Our long-term objectives are to determine how female athletes become more susceptible to non-contact ACL injury, prospectively identify those female athletes who are more susceptible to injury and to determine the underlying mechanistic cause(s) of increased risk at the biomechanical and biochemical levels and to optimize the effectiveness of treatments designed to prevent ACL injuries. Towards these goals, we propose to test the central hypothesis that the increases in lower extremity bone length and body mass that occur during puberty, without the neuromuscular performance spurt that most males demonstrate, will increase dynamic valgus, knee joint loading and injury risk in a subset of female athletes. It will also test the hypothesis that measures relating to dynamic valgus will prove predictive of ACL injury risk in high-risk female athletes. Specific Aim 1 will determine if following the onset of pubertal growth, increases in tibia and femur length and body mass, in the absence of increases in strength and recruitment of the musculature at the hip and knee that controls knee position and load, will lead to decreased neuromuscular control as measured by increased dynamic valgus in a subset of maturing female athletes. Specific Aim 2 will determine if objective biomechanical measures can predict relative ACL injury risk in female athletes. We hypothesize that a model that incorporates measures of dynamic valgus and variables that contribute to neuromuscular control of valgus (hip adduction moment) and increased knee joint load (knee abduction moment) will prove both sensitive and specific predictors of ACL injury risk in female athletes. These data should provide a foundation for approaching both the mechanistic questions underlying risk disparity, as well as increase our ability to direct high-risk athletes to effective, targeted interventions, which are proposed. Prevention of female rates from 5 times to equal males' would allow >30,000 females annually to continue the benefits of sports participation and to avoid the long-term complications of osteoarthritis, which may occur with a 10-fold greater incidence in the ACL-injured population.